Figure 24: The More We Know, the Faster We Go. As we have continued to amass knowledge about the inner workings of cancer and
technologies improve oand are developed, less time is required to develop new targeted therapies. In 1960, the BCR-Abl chromosomal
translocation in CML was first discovered. Because the necessary technologies and other fundamental knowledge were not yet in place, it took
over 40 years to develop and approve the first targeted agent, imatinib (Gleevec), which targets BCR-Abl. In 1978, overactive EGFR signaling was
associated with a subtype of lung cancer, and 26 years later, in 2004, the EGFR-inhibitor, gefitinib (Iressa), was FDA approved. More recently, in
2002, genome-wide screens first identified mutated B-Raf as a causative agent of nearly 50% of melanomas; the drug vemurafenib, which
targets it, was approved in 2011. Finally, the discovery of an ALK gene alteration in about 5% of lung cancers in 2007 led to the remarkably rapid
development and approval of the ALK inhibitor, crizotinib only four years later, in 2011. The time from target discovery to approval has declined
appreciably due to our increasing knowledge base and technical advances. It is important to note, however, that development and approval of
crizotinib had many advantages (such as jumpstarting development with a potent drug that had been previously tested in early phase trials for
other indications), and clinical development times cannot be reduced much further as clinical trials are required to assess safety and efficacy
steps. Adapted from (150).

Unfortunately, the decline in U.S. funding for biomedical research
comes at a time when other nations are giving a higher priority to
biomedical research and some are significantly increasing their
overall investments in science and technology. For example, China
has pledged to invest more than $300 billion in biomedical
research over the next five years (121). If current trends continue,
in only a few years, Chinese investment in life science research will
be double that of the U.S. A lack of commitment on the part of the
U.S. to prioritize and maintain its investment in science threatens
our Nation’s long-standing global leadership in innovation.

The declining NIH and NCI budgets are also creating an
environment where researchers face numerous disincentives to
continue in, or even enter into, research careers. It means the loss
of many young cancer investigators who will choose other careers
instead of scientific careers because of a lack of funding. These
disincentives are resulting in a loss of taxpayer-funded training and
are adversely affecting the Nation’s ability to maintain an optimal
workforce for the future of cancer research.

Furthermore, current fiscal austerity means that the success rates
for an investigator being awarded a research grant are diminished.
In fact, current investigators face an all-time low in funding
success rates, which has the detrimental effect of researchers
proposing lower risk ideas which are often less innovative (121).
This cycle creates missed opportunities to drive the science
forward, slowing the translation of benefit to the patient, which as a
country we cannot tolerate.

It is important to highlight that NIH funding of research across the
Nation results in a local economic impact that is at least double the
amount sponsored by the federal government. This multiplicative
effect works in reverse as well, and the threatened sequester cut of
$2.4 billion would likely drain twice that amount from local
economies. The ecosystem that produces biotech startups and new
jobs would be thrown in reverse at a time when job creation is a
social and economic priority.